Abstract The interactions of proteins with material surfaces is a fundamental aspect of biomedical technology, but little is known of the molecular-level mechanisms underlying the binding of proteins to biomineral surfaces. Even less is known of how proteins structurally adapt to non-native material surfaces. The aim of this R21 proposal is to apply a solid state NMR approach to elucidating the fundamental molecular-level nature of interactions between extracellular matrix (ECM) proteins, that have evolved to interact with biological materials like hydroxyapatite (Hap), and inorganic oxides that are used as coatings for dental implants and scaffolds. Salivary statherin is an enamel pellicle protein that inhibits hydroxyapatite (Hap) nucleation and growth, and is an adhesion site for oral bacteria involved in periodontal disease. Statherin is one of the few biomineralization proteins for which there is an experimentally constrained structure of the surface-bound form. In this project statherin will be used as a model to study how ECM proteins adapt structurally to implant material interfaces. We will focus on statherin?s structure/interactions with titanium (IV) oxide TiO2 , whose properties as an implant coating have been studied extensively. The anticipated outcome of this two year research effort is the development of a solid state NMR-based methodology which provides a rational, structure-based approach for predicting protein binding to and folding on inorganic oxide surfaces and other materials used as dental implant materials..